A digoxin derivative that potently reduces intraocular pressure: efficacy and mechanism of action in different animal models.

Glaucoma is a blinding disease. Reduction of intraocular pressure (IOP) is the mainstay of treatment, but current drugs show side effects or become progressively ineffective, highlighting the need for novel compounds. We have synthesized a family of perhydro-1,4-oxazepine derivatives of digoxin, the selective inhibitor of Na,K-ATPase.

Association of Familial Hyperkalemia and Hypertension with Proximal Renal Tubular Acidosis and Epileptic Seizures.

Introduction: Familial hyperkalemic hypertension (FHHt) is an inherited disease characterized by hyperkalemia, hypertension, and hyperchloremic acidosis (HCA). The primary defect is a hyperactive sodium chloride co-transporter, expressed in the renal distal tubule. FHHt is caused by mutation in either WNK1, WNK4, KLHL3, or Cul3.

A missense mutation converts the Na,K-ATPase into an ion channel and causes therapy-resistant epilepsy.

The ion pump Na,K-ATPase is a critical determinant of neuronal excitability; however, its role in the etiology of diseases of the central nervous system (CNS) is largely unknown. We describe here the molecular phenotype of a Trp931Arg mutation of the Na,K-ATPase catalytic α1 subunit in an infant diagnosed with therapy-resistant lethal epilepsy. In addition to the pathological CNS phenotype, we also detected renal wasting of Mg.

Revisiting the binding kinetics and inhibitory potency of cardiac glycosides on Na,K-ATPase (α1β1): Methodological considerations.

Introduction: Ouabain and digoxin are classical inhibitors of the Na,K-ATPase. In addition to their conventional uses as therapeutic agents or experimental tools there is renewed interest due to evidence suggesting they could be endogenous hormones. Somewhat surprisingly, different publications show large discrepancies in potency for inhibiting Na,K-ATPase activity (IC), particularly for the slow binding inhibitors, ouabain and digoxin.